靶向抑制脊髓5-羟色胺能通路对大鼠骨癌痛的影响  

EFFECT OF TARGETED INHIBITION OF SPINAL SEROTONERGIC PATHWAY ON BONE CANCER PAIN IN RATS

作　　者：刘希江[1] 王公明[1] 王岩[1] 牛新环[1] 张孟元[1] LIU Xi-Jiang WANG Gong-Ming WANG Yan NIU Xin-Huan ZHANG Meng-Yuan(Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China)

机构地区：[1]山东大学附属省立医院麻醉科,济南250021

出　　处：《中国疼痛医学杂志》2016年第10期749-753,共5页Chinese Journal of Pain Medicine

基　　金：山东省自然科学基金(编号:ZR2013HM066)

摘　　要：目的：探讨靶向抑制脊髓5-羟色胺能通路对大鼠骨癌痛的影响。方法：雌性SD大鼠70只,体重160~180 g,随机分组。骨癌痛组大鼠于胫骨骨髓腔注射Walker 256大鼠乳腺癌细胞悬液10μl制备癌痛模型。假手术组于骨髓腔注射D-hank＇s液10μl。大鼠造模后第10天行鞘内置管,第14天鞘内注射生理盐水或5-羟色胺选择性神经毒素5,7-DHT。鞘内给药前1天和给药后5天每天测定机械痛阈。鞘内给药后第3天取脊髓背角组织采用高效液相色谱法检测5-羟色胺含量。大鼠测痛结束后行胫骨X线摄片,观察肿瘤导致的骨破坏程度。结果：X线片显示骨癌痛大鼠术侧胫骨可见肿瘤生长导致的骨皮质大片缺损。与鞘内给予生理盐水的骨癌痛组大鼠相比,骨癌痛组大鼠鞘内给予5,7-DHT后机械性痛觉超敏显著缓解（P〈0.05）,缩爪持续时间明显缩短（P〈0.05）。与鞘内给予等体积生理盐水的大鼠相比,鞘内给予60μg的5,7-DHT可以显著的降低脊髓背角中5-羟色胺含量。结论：本实验证实了鞘内注射5,7-DHT选择性消除脊髓5-羟色胺可显著缓解骨癌痛大鼠的疼痛,说明脊髓背角中5-羟色胺含量的增加参与了大鼠骨癌痛的维持。Objective： To investigate the effect of targeted inhibition of spinal serotonergic pathway on bone cancer pain in rats. Methods： Seventy female SD rats, weighing 160 ~ 180 g, were randomly divided into five groups. Bone cancer pain rats were prepared by injection of 10 μl Walker 256 breast cancer cell suspension into the tibial bone marrow cavity. Sham operation rats were prepared by injecting 10 μl D-hank＇s solution into the tibial bone marrow cavity. Rats were intrathecally catheterized 10 days after modeling and normal saline or selective serotonin neurotoxin 5, 7-DHT were administrated from the fourteenth day after intrathecal catheterization. Mechanical pain threshold was measured every day from 1 day before and day 5 after intrathecal administration. Serotonin content in the spinal dorsal horn tissue was determined using high performance liquid chromatography 3 days after intrathecal administration. Tibial X-ray was used to observe the bone destruction caused by cancer after pain measurement. Results： X-ray showed large cortical bone defect on the surgery side of tibia caused by tumor growth in bone cancer pain rats. Compared with the rats receiving saline,mechanical allodynia was significantly alleviated in bone cancer pain rats after intrathecal administration of 5,7-DHT（P 〈0.05） and the paw withdrawal threshold in bone cancer pain rats was also significantly decreased（P 〈0.05）. Compared with the rats receiving saline,serotonin content in the spinal cord dorsal horn could be significantly reduced by intrathecal administration of 60 μg of 5,7-DHT. Conclusion： The present study showed that selective elimination of spinal serotonin through intrathecal injection of 5,7-DHT significantly relieved the pain of bone cancer pain rats, indicating that an increase in serotonin content in the spinal dorsal horn is involved in the maintenance of bone cancer pain.

关 键 词：5-羟色胺 骨肿瘤 疼痛 脊髓 

分 类 号：R614[医药卫生—麻醉学] R738.1[医药卫生—外科学]